Objective: To report an atypical case of suspected adult-onset Alexander disease presenting with unusual myoclonus-like episodes and progressive spastic gait, associated with a novel GFAP variant.

Background: Alexander disease is a rare GFAP-related disorder with a broad clinical spectrum. Adult-onset cases typically present with bulbar symptoms, spasticity, ataxia, or gait impairment, often accompanied by characteristic medullary abnormalities on brain MRI. Myoclonus-like paroxysmal episodes are rarely emphasized as a presenting feature, and expansion of the genotypic and phenotypic spectrum remains important.

Method: We reviewed the clinical presentation, neurological examination, neuroimaging findings, and genetic test results of a 54-year-old woman with progressive gait disturbance and paroxysmal unilateral involuntary movements.

Results: A 54-year-old woman presented with a 3-year history of intermittent involuntary movements of the left hand, described as tremulous or myoclonus-like episodes, occurring 2–3 times daily and lasting about 1 hour. These episodes were accompanied by paresthesia without impaired awareness. Gait disturbance developed from the same period. There was no known family history. At presentation, the abnormal movements had become infrequent after treatment with clonazepam and baclofen at another clinic. Neurological examination revealed spastic gait, more prominent in the left leg. Electroencephalography and nerve conduction studies showed no significant abnormalities. Brain MRI demonstrated signal hyperintensity in the medial medulla and a medullary cleft, suggestive of adult-onset Alexander disease. Next-generation sequencing identified a heterozygous GFAP variant, c.974A>G, which has not been previously reported. However, segregation analysis could not be performed because both parents were deceased, limiting further assessment of pathogenicity.

Conclusion: This case highlights that adult-onset Alexander disease may present with unusual unilateral myoclonus-like episodes in addition to progressive spastic gait. In such cases, characteristic medullary MRI findings can provide an important diagnostic clue, and further accumulation of genotype-phenotype data is needed to clarify the significance of novel GFAP variants.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/adult-onset-alexander-disease-with-paroxysmal-myoclonus-like-episodes-and-a-novel-gfap-variant/